There is considerable evidence indicating that the secretory defect in non-insulin-dependent-diabetesmellitus is contributed to by a mis-regulation of beta cell intracellular pH, and can be corrected through pharmacological manipulation of intracellular pH. These hypotheses will be tested by comparing the regulation of intracellular pH in islets from healthy and diabetic animals, and monitoring insulin secretion from defective islets after pharmacological alteration of intracellular pH. The mechanisms of how intracellular pH influences insulin secretion is not known, and this will be investigated by monitoring changes in the production of reducing equivalents parallel to changes in intracellular pH and insulin secretion.